Anti-aging research has continued to advance in recent years. Somatic aging is a major cause of skin aging from a macroscopic viewpoint, but other causes such as oxidation, dryness and sunlight (ultraviolet rays) are also direct factors related to skin aging. The specific phenomenon of skin aging is known to be associated with cellular damage due to reduction in mucopolysaccharides including hyaluronic acid, collagen crosslinking reaction and ultraviolet rays.
A great deal of research is also being carried out with the aim of inhibiting or improving, e.g., skin wrinkles, fine wrinkles, and sagging, caused by skin damage or skin aging due to ultraviolet exposure. As a result, efficacy has been demonstrated for promoting hyaluronic acid production (JP2001-163794A: Patent document 1), suppressing production and activation of matrix metalloproteinases (MMP) (JP2000-503660X: Patent document 2), promoting production of collagen and inhibiting esterase activation (JP-H11-335235B: Patent document 3), suppression of angiogenesis (WO03/84302A: Patent document 4), and suppressing lymphangiectasis (K. Kajiya et al., Am. J. Pathol., 2006, 169(4): 1496-1503: Non-patent document 1).
Such research is largely divided into efforts to prevent and improve fine wrinkles, with focus on the epidermis or epidermal cells, and efforts to prevent and improve large wrinkles, with focus on suppressing changes in the dermis including blood vessels or lymphatic vessels. Propagation of changes in the epidermis to the dermis leads to alteration of the dermis, including the blood vessels and lymphatic vessels, and heparanase is intricately involved in the process. It has in fact been demonstrated that a significant anti-wrinkle effect is obtained by coating a fine wrinkle model with a heparanase inhibitor (PCT/JP2009/056717).